There exists each class of immunoglobulins such as IgG, IgA, IgM, IgD and IgE. IgM antibodies are first raised in response to the stimulation of an antigen, and rapidly disappear owing to the short half life thereof. Thus, they are gradually replaced with IgG. Allogenic hemagglutinin, rheumatoid factors, heterophile antibodies and cold agglutinin predominantly belong to this IgM (Rinsho Kensaho Teiyou (Guidebook on laboratory test), Kanehara & Co., Ltd., 31st. Edition, 1998, p. 820).
In cases of infectious diseases, it is diagnostically useful to measure both specific antibody titers of the serum in the initial stage of the infection and of the serum in the stage convalescent, pairwise (Guidebook on laboratory test), Kanehara & Co., Ltd., 31st. Edition, 1998, p. 808). For example, a method for detecting IgM has been reported for the purpose of determining the infection with human cytomegalovirus (HCMV) (Japanese Translation Provisional Publication No. Hei10-502253). However, there has not been disclosed any method for concurrently detecting IgG and IgM.
Class switching from IgM to IgG of immunoglobulins has been generally known to be achieved within approximately one month following the appearance of the IgM. However, many of the natures of candidate substances which may be an antigen have been unknown, and a period of time required for the class switching of an immunoglobulin as well as other characteristics have not yet been elucidated in many aspects.
For example, in connection with Borna disease which is an immune related neurologic syndrome of which causative virus is Borna disease virus (hereinafter, referred to as “BDV”), many matters have not been elucidated yet. Borna disease is a viral encephalomyelitis caused in a horse through the four seasons in Germany as well as surrounding nations thereof. It exhibits symptoms such as cerebral palsy, affective disorder and the like, which may be lethal when it follows the acute process. When a rat is experimentally infected with this virus, a polyphasic syndrome characterized by hyperkinesia, stereotyped behavior, dyskinesia and ataxia is developed (O. Narayan et al., Science, 220:1401-1403 (1983)).
BDV has been known of its pathogenicity toward horses that are the natural hosts thereof, and the existence of an antibody that reacts with BDV was indicated in the serum of a patient suffering from a mental disorder in 1985, suggesting the probability of pathogenesis also toward humans. Infectious epidemiologic studies of BDV shall greatly contribute to understandings of the mental disorders. Recently, a BDV gene has been found in hemocytes including gene clusters of mental disorders with a certain frequency.
Because BDV proliferates at just a low titer, purification for executing an analysis is difficult. Diagnoses of BDV infection have been carried out through detecting the appearance of clinical symptoms that are common in this disease, and detecting a serum antibody that detects a viral protein in an infected cell by an indirect immunofluorescence technique (IFT) (G. Pauli et al., Zbl. Vet. Med. [B], 31: 552-557 (1984)), Western blot, immunoprecipitation or the like. Operation in these methods is complicated, therefore, it is difficult to use those in a mass investigation of a group of humans or livestocks.
The sequence of BDV has been already elucidated, and a method for detecting an anti-BDV antibody by an ELISA method has been reported, where p23, recp23, p40 and recp40 antigens are used (Japanese Patent Provisional Publication No. 2001-190288). In addition, a test method involving the determination of a BDV specific circulating immune complex (CIC) in plasma was also reported, where p40 and p24 antigens have been used (Japanese Translation Provisional Publication No. 2002-500363). Moreover, a method for detecting an antibody by magnetic beads in which an antigen polypeptide including a specific amino acid sequence selected from p40 and p24 regions was also reported (Japanese Patent Provisional Publication No. Hei11-180998)
However, characteristic features of BDV have been still far from being sufficiently elucidated, and many points remain unknown in connection with the period when an antibody to BDV is raised or with the accurate method for detecting an antibody. Accordingly, development of more accurate method for detecting an antibody has been desired.
An object of the present invention is to provide a reagent for detecting an anti-BDV antibody for more accurately carrying out the examination of an antibody to a exogenous antigen, particularly BDV, and to provide a method for detecting an anti-BDV antibody in which the reagent is used.